E5090 is a newly synthesized orally active inhibitor of IL-1 generation without cyclooxygenase inhibiting activity form. Orally administered E5090 is rapidly changed to the pharmacologically active, DA-E5090, by deacetylation. On the in vitro systems using human monocytes and rats peritoneal macrophages stimulated with LPS, DA-E5090 dose-dependently inhibited the IL-1 generation due to the inhibition of IL-1mRNA expression.
On the in vivo systems of IL-1 generation in rat air-pouch models induced by nonallergic or allergic stimuli, orally administered E5090 dose-dependently inhibited the generation of IL-1 activity and the chronic granuloma formation similar to steroidal anti-inflammatory drug, prednisolone. On the other hand, indomethacin had no effects on both IL-1 generation and granuloma formaton in spite of the perfect inhibition of prostaglandin E2 generation. The quantitative measurements of other inflammatory cytokines such as TNF and IL-6 suggest that IL-1 may be a main mediator for granuloma formation in these animal models. In adjuvant arthritis, E5090 suppressed not only the paw inflammation but also the in creases in ESR and peripheral blood leucocyte numbers, being similar to prednisolone in these respects, but different from indomethacin.
These results suggest that the inhibitor of IL-1 generation may show steroid-like anti-inflammatory effects.

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Mast cells have two subtypes, connective tissue mast cells (CTMC) and mucosal mast cells (MMC) . The role of CTMC in immediate type hypersensitivity is well recognized, whereas in vivo role of MMC is unknown yet. MMC differ from CTMC in sensitivity to secretagogues and in amount of mediators released. Many CTMC constantly distribute in connective tissues, while MMC appear only in specific conditions like intestinal parasite infection and proliferate depending on T-cells. It is, therefore, suggested that MMC have a distinct functional role from that of CTMC. Athymic nude mice show no MMC response to intestinal parasite infection and can not expel the worms. When IL-3, a mast cell growth factor, was repeatedly injected into KSN nude mice, number of MMC was markedly increased in the intestine.
To see if the induced MMC show any effects on expulsion, IL-3 was injected into KSN nude mice infected with a nematode, Strongyloides ratti which are usually not expelled from the nude mice. As a result, S. ratti were completely expelled from the small intestine of the IL-3 treated-nude mice with markedly increased number of intestinal MMC. MMC induced with IL-3 probably effect on the expulsion of S. ratti. Mechanism of expressing the function of MMC in vivo is discussed.

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Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increased neutrophil C3bi-receptor expres-sion and adherènce and rapidly primed neutrophils to enhance O^-₂ release and membrane depolarization stimulated by chemotactic peptide, plant lectins and Ca²⁺ ionophore, but not by phorbol ester. Direct triggering of O^-₂ release in suspended neutrophils was also provoked by GM-CSF, but not by G-CSF. The biological activity was greater in non-glycosylated GM-CSF than in glycosylated GM-CSF, whereas it was identical in glycosylated and non-glycosylated G-CSFs. Direct stimulation and priming by GM-CSF were greater than those by G-CSF in all parameters tested, and the combined addition of the optimal concentrations of G-CSF and GM-CSF always resulted in the effects of GM-CSF alone.
These findings indicate that the effects of G-CSF and GM-CSF are partly similar, but qualitatively and quantitatively different from each other.

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The mechanism of platelet-derived growth factor (PDGF) gene expression was studied using blood monocytes. Resting monocytes constitutively transcribed both PDGF-A and -B genes. Lipopolysaccharide (LPS) -stimulation markedly increased both PDGF-A and -B gene transcription rates. Consistent with the increased transcription rates, PDGF-A mRNA increased continuously after the stimulation. In contrast, PDGF-B mRNA immediately increased and then decreased after the stimulation. Cycloheximide, a protein synthesis inhibitor, increased the levels of PDGF-A and -B mRNA in resting and LPS-stimulated monocytes without affecting PDGF-A and -B gene transcription rates, suggesting de novo synthesized protein factor (s) are involved in the instability of PDGF mRNA. Polymerase chain reaction revealed that resting monocytes expressed only short PDGF-A mRNA species (exon I-V+VII), but LPS-stimulated monocytes expressed long PDGF-A mRNA species (exon I -VII) as well. Both resting and LPS-stimulated monocytes expressed only one PDGF-B mRNA species (exon I-VII) .
LPS-stimulated monocytes released the increased amount of PDGF, and the release of PDGF was inhibited by cycloheximide, suggesting the released PDGF is derived from de novo synthesized PDGF protein. Together, these observations indicate that PDGF gene expression is regulated at the level of PDGF gene transcription, stability and splicing of PDGF mRA, and synthesis of PDGF protein.

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A0dministration of a large doses (500-3, 000mg/kg, i.p.) of new quinolone antibacterials (NQs) such as norfloxacin (NFLX), ofloxacin (OFLX), enoxacin (ENX), ciprofloxacin (CPFX) and lomefloxacin (LFLX) caused convulsant death in mice. LD50 values (mg/kg) of NQs were 698 for LFLX, 805 for OFLX, 1064 for NFLX, 1165 for CPFX and 3600 for ENX, respectively. These neuroexitable effects of NQs were amplified by concomitant intake of 4-biphenylacetic acid (BPAA) as an active metabolite of fenbufen, keto-profen and naproxen, resulting in tonic and clonic convulsions and convulsant death. In this case, the order of the dose of NQ on inducing convulsion was expressed as follows; ENX<LFLX<NFLX<CPFX<OFLX. The CNS activity of NQ, except CPFX, was amplified by naproxen, more significantly than by ketoprofen. CPFX was sensitive to ketoprofen. ENX in the presence of NSAID demonstrated an affinity for GABA receptor.
Thus, GABA-ergic mechanism may be responsible for the effect of NSAID on the CNS activity of NQ. However, it was difficult to find a certain relation between inhibition of GABA binding and convulsion.

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Rat α₂-AP was isolated from the sera of turpentine induced inflammatory rats by an immunoaffinity chromatography and the inhibitory activity of α₂-AP on rat adjuvant arthritis was investigated.
Rat α₂-AP administration inhibited both the primary inflammation and the secondary inflammation (adjuvant arthritis) induced by Freund's complete adjuvant. The inhibitory effects of α₂-AP on adjuvant arthritis were found to be enhanced by inhibiting the primary inflammatory processes.

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Renal scars have been considered to occur in later stages of chronic pyelonephritis. In our experimental pyelonephritis models bacteria which possessed mannose-sensitive (MS) pili promoted renal scarring following inoculation to the renal parenchyma. Polyethylene glycol modified superoxide dismutase (PEGSOD), 2-0-octadecyl ascorbic acid (CV3611), dapsone and steroid significantly suppressed scarring when parenterally administered during the early stage on kidney infection. These had no effect on bacterial growth in the kidney.
These findings suggest that the superoxide and other active oxygens play an important role in renal scarring following infection and that PEG-SOD, CV 3611, dapsone and steroid may be agents capable of preventing renal scarring.

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To evaluate the effect of a newly developed immunomodulating drug, CCA in the early stage of RA, we examined histological features, with the aid of immunohistochemical markers, in the synovial tissue of the knee joint of RA patients (within one year after onset of disease) on two occasions, that is, before and after the administration of CCA at the dose of 240 mg per day for 6 to 24 weeks. In 10 cases examined, 3 of them took as favorable course and 3 took a fair course and the remaining did not change by the administration of CCA. Immunostaining of tissues from the improved patients revealed that (1) the total number of inflammatory cells were decrease after CCA treatment, (2) the accumulation of lymphocytes, mostly B cells, in the synovia, was not detected prior to CCA administration.
Although it was impossible to count the number of HLA/DR positive cells which were consisted of various kinds of cells such as macrophages, B lymphocytes, a part of synovial lining cells, T lymphocytes and interstitial cells, the quantitative change of these cells was parallel to the total cell number in synovial tissues.

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Sympathetic nerve block, periganglionic methylprednisolone injection and antiviral agent therapy have been adopted for treatment of herpetic neuralgia and prevention of post-herpetic neuralgia. Although such therapies are applied at the early stages of the disease, many aged patients suffer from post herpetic neuralgia. During the past five years, 24 post-herpetic neuralgia patients were treated with intravenous prostaglandin E₁ (120-180 μg/week) . The pain was reduced at various degrees in all cases. While 13 patients out of 24 had neuralgia in the trigeminal region (group T), the other 11 patients were suffering in the spinal nerve region (group S) . 11 cases in group T and 5 cases in group S exhibited excellent improvement. 2 cases in group T and 6 in group S showed in moderate improvement. Among all 24 cases, 5 cases in group T (group Tp) and 4 in group S (group Sp) received intravenous prostaglandin E₁ only. All of group Tp responded excellently to prostaglandin E₁, however 3 cases in group Sp revealed only moderate improvement and one case showed no improvement at all. There was a significant difference between group Tp and Sp.
The results indicate there is a correlation between the area being treated and the effectiveness of the treatment. Notably the treatment of intravenous prostaglandin E₁ was extremely effective when applied to the trigeminal area.

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In order to confirm efficacy, safety and utility of mizoribine (MZR) for treatment of rheumatoid arthritis, we conducted a 24 weeks double-blind controlled study using lobenzarit disodium (CCA) as a control drug and obtained the following results.
(1) The study involved 72 cases for MZR group and 77 cases for CCA group. There were no significant differences in patients' backgrounds between the two groups.
(2) Final global improvement rate was evaluated as “improvement” or more in 26.8% (15/56) for MZR group vs. 12.3% (8/65) for CCA group, “slight improvement” or more in 55.4% (31/56) for MZR group VS. 36.9% (24/65) for CCA group. There was no significance for any of these differences.
(3) The incidence of side effects of MZR group was 31.9% and that of CCA group was 48.7%. No serious side effect was observed in both groups.
(4) Radiographic films of 41 patients participating in this study were evaluated in a random order by two readers. Only in the CCA group (21 patients) was a statistically significant increase in the mean value of erosion score as well as damage score. These results show that MZR do retarded radiographic progression of joint destruction in the treatment of rheumatoid arthritis.
(5) The utility of MZR group was superior to CCA group. These results indicate that mizoribine is a useful drug for treatment of rheumatoid arthritis.

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